These investigations addressed the problems of sudden cardiac death. The three main objectives pursued included development of methods for identifying the subject at risk, definition of predisposing mechanisms, and introduction of measures for protecting against ventricular fibrillation (VF). Both animal and human investigations were carried out. Animal studies resulted in the following findings: a) The induction of repetitive extrasystoles was shown to provide a reliable measure of vulnerability in the ischemic as well as the normal heart; b) A biologic model was developed to study the role of platelets in altering electrical stability of the heart during coronary artery stenosis; c) The prostaglandins E1 and I1 were shown to exert a significant antifibrillatory influence by preventing intracoronary platelet aggregation during coronary stenosis; d) Endogenous substances including insulin and the essential amino acid, tyrosine, were found to exert a potent antifibrillatory action; and e) We demonstrated the possibility of identifying the site of origin of ectopic activity by radionuclide techniques. Clinical studies showed that a multiple ventricular response is a consistent finding among patients who have experienced sudden death due to VF and that individualized antiarrhythmic drug treatment resulting in abolition of such a response protects against recurrence of VF. Drug studies are ongoing and we have concluded evaluation of mexiletine and amiodarone.